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Identification of a 2 Mb human ortholog of Drosophila eyes shut/spacemaker that is mutated in patients with retinitis pigmentosa.
Am. J. Hum. Genet. 83, 594-603 (2008)
In patients with autosomal-recessive retinitis pigmentosa (arRP), homozygosity mapping was performed for detection of regions harboring genes that might be causative for RP. In one affected sib pair, a shared homozygous region of 5.0 Mb was identified on chromosome 6, within the RP25 locus. One of the genes residing in this interval was the retina-expressed gene EGFL11. Several genes resembling EGFL11 were predicted just centromeric of EGFL11. Extensive long-range RT-PCR, combined with 5'- and 3'- RACE analysis, resulted in the identification of a 10-kb transcript, starting with the annotated exons of EGFL11 and spanning 44 exons and 2 Mb of genomic DNA. The transcript is predicted to encode a 3165-aa extracellular protein containing 28 EGF-like and five laminin A G-like domains. Interestingly, the second part of the protein was found to be the human ortholog of Drosophila eyes shut (eys), also known as spacemaker, a protein essential for photoreceptor morphology. Mutation analysis in the sib pair homozygous at RP25 revealed a nonsense mutation (p.Tyr3156X) segregating with RP. The same mutation was identified homozygously in three arRP siblings of an unrelated family. A frame-shift mutation (pPro2238ProfsX16) was found in an isolated RP patient. In conclusion, we identified a gene, coined eyes shut homolog (EYS), consisting of EGFL11 and the human ortholog of Drosophila eys, which is mutated in patients with arRP. With a size of 2 Mb, it is one of the largest human genes, and it is by far the largest retinal dystrophy gene. The discovery of EYS might shed light on a critical component of photoreceptor morphogenesis.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
human Ortholog; Drosohila; eyes shut/spacemaker; Retinitis Pigmentosa
ISSN (print) / ISBN
0002-9297
e-ISSN
1537-6605
Zeitschrift
American Journal of Human Genetics, The
Quellenangaben
Band: 83,
Heft: 5,
Seiten: 594-603
Verlag
Elsevier
Verlagsort
New York, NY
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Human Genetics (IHG)